Mild Clinical and Biochemical Phenotype in Two Pat

Authors: M Casado M M O’Callaghan R Montero C PérezCerda B Pérez P Briones E Quintana J Muchart A Aracil M Pineda R Artuch

Publish Date: 2011/10/20

Volume: 11, Issue: 2, Pages: 557-563

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Abstract

Phosphomannomutase 2 deficiency PMM2CDG patients may present as mild phenotypes with the cerebellum frequently involved In those cases falsenegative results in screening may occur when applying conventional biochemical procedures Our aim was to report two patients with a diagnosis of PMM2CDG presenting with mild clinical phenotype Patient 1—at 9 months of age she presented with just psychomotor delay tremor hypotonia and slight lipodystrophy Patient 2—she presented at 8 months of age with psychomotor delay hand stereotypes hypotonia convergent bilateral strabismus and tremor but no lipodystrophy Routine biochemical parameters including blood count clotting factors proteins and thyroid hormone were normal in both cases Cranial MRI evidenced mild cerebellar atrophy with moderate vermis hypoplasia In case 1 sialotransferrin pattern showed very slightly increased disialotransferrin with no asialotransferrin and in case 2 the transferrin pattern was impaired in the first study but nearly normal in the second Nevertheless in all the samples quantification of the patterns obtained by capillary zone electrophoresis analysis gave results out of the control range High residual PMM2 activity was observed in both cases and the genetic analysis showed that patient 1 was heterozygous for c722GC pC241S and c368GA pR123Q mutations and patient 2 showed the c722GC and the c470TC pF157S mutations in the PMM2 gene We would like to stress the importance of the use of sensitive semiquantitative methods of screening for CDG in order to achieve early identification of patients with mild phenotypes Intentional tremor was an atypical but remarkable clinical feature in both cases and the global cerebellar atrophy with vermis hypoplasia reinforced the early clinical suspicion of a PMM2CDG diseaseThis work was supported by grants from the Fondo de Investigación Sanitaria FIS PI080663 PI080307 and PI10/00455 The CIBERER is an initiative of the Instituto de Salud Carlos III ISCIII MICIN Spain RArtuch and M Casado are supported by the program Intensificacion de la Actividad Investigadora ISCIII R Montero and MM O’Callaghan were funded by the CIBERER

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